Isoprostaglandin E2 type-III (8-iso-prostaglandin E2) evoked contractions in the human internal mammary artery

doi:10.1016/S0024-3205(01)01032-3

Life Sciences

Volume 68, Issue 21, 13 April 2001, Pages 2405-2413

https://doi.org/10.1016/S0024-3205(01)01032-3 Get rights and content

Abstract

E₂-isoprostanes are recently discovered compounds that are produced in vivo from free radical-catalysed peroxidation of arachidonic acid. One such compound whose formation is favoured by this mechanism is isoprostaglandin E₂ type III (iPE₂-III, also named 8-iso-prostaglandin E₂ or 15-E_2t-isoprostaglandin). The aim of this study was to evaluate the vasomotor properties of iPE₂-III in isolated human internal mammary artery.

In organ bath, iPE₂-III was approximately 10 times more potent than isoprostaglandin F₂α-III and 27 times more potent than prostaglandin E₂, whereas both isoprostaglandin F₃α-III and 15-epi-isoprostaglandin F₂α-III induced weak contractions. The responses to iPE₂-III were inhibited in a concentration-dependent manner by the thromboxane A₂ receptor antagonist GR 32191 (3.10⁻⁹ to 3.10⁻⁷ M). Indomethacin, a cyclooxygenase inhibitor and phosphoramidon, an endothelin converting enzyme inhibitor, did not affect iPE₂-III response.

These data shows that iPE₂-III is a more potent vasoconstrictor of human internal mammary arteries than isoprostaglandin F₂α-III. These effects are mediated by TP receptors, but involve neither cyclooxygenase products nor endothelins. iPE₂-III production may induce more pronounced vasomotor effects than isoprostaglandin F₂α-III in situations of oxidative stress, and in particular may modulate internal mammary artery tone following coronary bypass surgery.

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Cited by (17)

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2017, Progress in Lipid Research
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For instance, 15-E2t-IsoP, one of the two IsoPs (together with 15-F2t-IsoP) that was available for biological testing in the early years, has shown to be a renal vasoconstrictor that caused a reduction in the glomerular capillary pressure and filtration rate at low nanomolar range [129]. This 15-E2t-IsoP was even more potent than 15-F2t-IsoP in activation of TP and EP3 receptors [130,131]. Furthermore, 15-E2t-IsoP has been reported to activate intestinal epithelial cells contraction [132], stimulate the binding of monocytes to the endothelial cells [133], exert contractile activity on gastrointestinal smooth muscle [134] and act as a regulator of the airways [135,136].
Since the beginning of the 1990's diverse types of metabolites originating from polyunsaturated fatty acids, formed under autooxidative conditions were discovered. Known as prostaglandin isomers (or isoprostanoids) originating from arachidonic acid, neuroprostanes from docosahexaenoic acid, and phytoprostanes from α-linolenic acid proved to be prevalent in biology. The syntheses of these compounds by organic chemists and the development of sophisticated mass spectrometry methods has boosted our understanding of the isoprostanoid biology. In recent years, it has become accepted that these molecules not only serve as markers of oxidative damage but also exhibit a wide range of bioactivities. In addition, isoprostanoids have emerged as indicators of oxidative stress in humans and their environment. This review explores in detail the isoprostanoid chemistry and biology that has been achieved in the past three decades.
Decreased vasorelaxation induced by iloprost during acute inflammation in human internal mammary artery
2017, European Journal of Pharmacology
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In addition, the contraction induced by the EP3 agonist (sulprostone) was more potent than the EP1 agonist (17-phenyl-PGE2). These latter observations confirm that still under Inflammatory conditions, the EP3 receptor is mainly implicated during the vasoconstriction induced by PGE2 in IMA as it has been shown in previous studies using fresh healthy IMA preparations (Cracowski et al., 2001; Foudi et al., 2011; Tanaka et al., 2004; Wiley and Davenport, 2002). In addition, our study suggests that the expression of receptors activated by PGE2 and TxA2 are not modified during acute inflammation.
Cyclooxygenase-2 (COX-2) induction in human internal mammary arteries (IMA) under inflammatory conditions has been associated with attenuated norepinephrine (NE)-induced vasoconstriction. This effect was associated with increased prostaglandin (PG) E₂ and prostacyclin (PGI₂) releases. The present study was designed to assess the role of these PG and their receptors (EP and IP, respectively) on the vascular reactivity during acute inflammation. Isolated IMA were cultured in the absence (Control conditions) or presence (Inflammatory conditions) of both interleukin-1 beta (IL-1β) and lipopolysaccharide (LPS). The vasorelaxation and the increased content of cyclic adenosine monophosphate (cAMP) induced by iloprost, a PGI₂ analogue, were significantly reduced under inflammatory conditions and restored in preparations cultured with the IP antagonist (CAY10441). Decreased cAMP levels under inflammatory conditions are due to at least increased phosphodiesterase (PDE) 4B expression. On the other hand, PGE₂, thromboxane analogues and EP agonists-induced vasoconstrictions were not affected under inflammatory conditions. No vasorelaxation was observed with PGD₂, PGE₂ or the EP2/4 agonists in pre-contracted IMA. Finally, using RT-qPCR and immunohistochemistry, the COX-2, IP receptor and PGI₂ synthase (PGIS) were detected. A significant increase of COX-2 and moderate increase of IP mRNA expression was observed under inflammatory conditions, whereas PGIS mRNA level was not affected. This study demonstrates that PGI₂/IP receptor signalling and PGI₂-induced relaxation are impaired in human IMA during acute inflammation, whereas the responses induced by other prostanoids are not affected. These results could explain some of the mechanisms of vascular dysfunction reported in inflammatory conditions.
Lipid peroxidation generates biologically active phospholipids including oxidatively N-modified phospholipids
2014, Chemistry and Physics of Lipids
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Thus, it seems reasonable to speculate that IsoLG-PC and IsoLG-PE may invoke at least some, if not most, of the same effects on proteins as unesterified IsoLG. Unesterified 15-F2-IsoP and 15-E2-IsoP are potent vasoconstrictors with 100 nM being sufficient to induce this effect, which can be blocked by thromboxane A2 (TxA2) receptor (TP) antagonists (Cracowski et al., 2001; Hoffman et al., 1997; Mohler et al., 1996; Morrow et al., 1994; Mueed et al., 2008; Wagner et al., 1997). Similarly, unesterified 15-F2-IsoP induces smooth muscle cell contraction and bronchoconstriction in the lung and this effect is blocked by TP antagonists (Bernareggi et al., 1998).
Peroxidation of membranes and lipoproteins converts “inert” phospholipids into a plethora of oxidatively modified phospholipids (oxPL) that can act as signaling molecules. In this review, we will discuss four major classes of oxPL: mildly oxygenated phospholipids, phospholipids with oxidatively truncated acyl chains, phospholipids with cyclized acyl chains, and phospholipids that have been oxidatively N-modified on their headgroups by reactive lipid species. For each class of oxPL we will review the chemical mechanisms of their formation, the evidence for their formation in biological samples, the biological activities and signaling pathways associated with them, and the catabolic pathways for their elimination. We will end by briefly highlighting some of the critical questions that remain about the role of oxPL in physiology and disease.
Isoprostanes constrict human radial artery by stimulation of thromboxane receptors, Ca<sup>2+</sup> release, and RhoA activation
2008, Journal of Thoracic and Cardiovascular Surgery
Radial artery vasospasm remains a potential cause of early graft failure after coronary bypass graft surgery, despite pretreatment with α-adrenergic or calcium channel blockers. We examined the roles of isoprostanes and prostanoid receptors selective for thromboxane A₂ in the vasoconstriction of human radial arteries.
Human radial arterial segments were pretreated intraoperatively with verapamil/papaverine or nitroglycerine/phenoxybenzamine, or not treated. In the laboratory, we measured isometric contractions in ring segments, vasoconstriction in pressurized segments, and changes in [Ca²⁺] and K⁺ currents in single cells.
Although phenoxybenzamine eliminated adrenergic responses, the isoprostane 15-F_2t-IsoP and 2 closely related E-ring molecules (15-E_1t-IsoP and 15-E_2t-IsoP) still evoked powerful contractions; 15-E_2t-IsoP was approximately 10-fold more potent than the other 2 agents. Responses were mediated through thromboxane receptors because they were sensitive to ICI-192605. Furthermore, they were sensitive to the Rho-kinase inhibitors Y-27632 or H-1152 (both 10⁻⁵ mol/L) or to cyclopiazonic acid (which depletes the internal Ca²⁺ pool), but not to nifedipine. In single cells, 15-E_2t-IsoP elevated [Ca²⁺]_i and suppressed K⁺ current.
Isoprostanes accumulate after coronary artery bypass graft surgery, yet none of the currently available antispasm treatments for radial artery grafts is effective against isoprostane-induced vasoconstriction. It is imperative that more specific treatment strategies be developed. We found that isoprostane responses in radial arteries are mediated by prostanoid receptors selective for thromboxane A₂ with activation of Rho-kinase and release of Ca²⁺. Pretreatment of radial artery grafts with Rho-associated kinase inhibitors may potentially reduce postoperative graft spasm. Clinical studies to test this are indicated.
Isoprostanes, biomarkers of lipid peroxidation in humans. Part 3: Biomarkers and mediators in vascular physiology and disease
2005, Pathologie Biologie
Les F₂-isoprostanes de la série 15 induisent une vasoconstriction sur la plupart des territoires vasculaires chez l'animal comme chez l'homme. Cette vasoconstriction est liée à la stimulation des récepteurs au thromboxane, et peut être modulée par l'endothélium. De plus, la 15-F_2t-IsoP induit une prolifération des cellules musculaires lisses et une adhésion monocytaire sur les cellules endothéliales. Les isoprostanes E₂ sont plus puissants, mais sont moins facilement détectables dans les liquides biologiques. En condition clinique, les taux d'isoprostanes sont élevés dans le cadre de certaines pathologies vasculaires impliquant l'athérosclérose, l'ischémie–reperfusion ou l'inflammation. Il existe une corrélation entre la sévérité de l'insuffisance cardiaque et de l'hypertension artérielle pulmonaire et les taux d'isoprostanes, posant la question d'un intérêt potentiel pronostique de ces biomarqueurs. Une question à résoudre est de savoir si les effets délétères observés in vitro peuvent être observés chez l'homme à des concentrations physiologiques, et de déterminer si ces effets peuvent contribuer à la physiopathologie de certaines pathologies vasculaires.
The 15-series F₂-isoprostanes mediate vasoconstriction in different vascular beds and species. This contraction is mediated by the thromboxane receptors stimulation, and may be modulated by the endothelium. Furthermore, 15-F_2t-IsoP induces smooth muscle cells mitogenesis and monocyte adhesion to endothelial cells. Some 15-series E₂-isoprostanes are more potent than F₂-isoprostanes. In clinical studies, 15-F_2t-IsoP levels are increased in vascular disorders involving atherosclerosis, ischemia–reperfusion and inflammation. F₂-isoprostane levels correlate to the severity of heart failure and pulmonary hypertension, raising the potential prognostic interest of these biomarkers. Whether the effects observed in vitro are observed consistently in vivo at physiological concentrations and whether these effects contribute to pathological states in vivo is still debated.
Vasoconstrictor effects of 8-iso-prostaglandin E <inf>2</inf> and 8-iso-prostaglandin F <inf>2α</inf> on human umbilical vein
2004, European Journal of Pharmacology
The present study was undertaken to determine whether 8-iso-prostaglandin E₂ and 8-iso-prostaglandin F_2α posses contractile action on human umbilical vein and to evaluate the possible involvement of prostanoid TP receptors in this effect. Human umbilical vein rings were mounted in organ baths and concentration–response curves to 8-iso-prostaglandin E₂ or 8-iso-prostaglandin F_2α were constructed. Both isoprostanes evoked concentration-dependent contraction. 8-iso-prostaglandin E₂ (pEC₅₀=6.90±0.03) was significantly more potent than 8-iso-prostaglandin F_2α (pEC₅₀=6.10±0.04). However, both isoprostanes were equieffective. The prostanoid TP receptor antagonists, ICI-192,605 (4-(Z)-6-(2-o-Chlorophenyl-4-o-hydroxyphenyl-1,3-dioxan-cis-5-yl)hexenoic acid) and SQ-29548 (7-[3-[[2-[(phenylamino)carbonyl]hydrazino]methyl]-7-oxabicyclo[2.2.1]hept-2-yl]-[1S(1α,2α(Z),3α,4α)]-5-Heptenoic acid) produced a competitive rightward shift of 8-iso-prostaglandin E₂ concentration–response curves with pK_B values of 8.91±0.04 and 8.07±0.07, respectively. When ICI-192,605 (1 nM) and SQ-29548 (10 nM) were evaluated against 8-iso-prostaglandin F_2α they produced a parallel rightward displacement of 8-iso-prostaglandin F_2α concentration–response curves without affecting the maximum responses giving pA₂ values of 9.02±0.12 and 8.26±0.13, respectively. In conclusion, the present study describes for the first time the vasoconstrictor action of 8-iso-prostaglandin E₂ and 8-iso-prostaglandin F_2α in human umbilical vein. Furthermore, the affinity values obtained with ICI-192,605 and SQ-29548 provide strong pharmacological evidence of prostanoid TP receptors involvement in this effect.

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Original articlesIsoprostaglandin E2 type-III (8-iso-prostaglandin E2) evoked contractions in the human internal mammary artery

Abstract

Original articles
Isoprostaglandin E₂ type-III (8-iso-prostaglandin E₂) evoked contractions in the human internal mammary artery